ABSTRACT
Whilst the physical and chemical properties of nanoparticles in the gas or idealized solvent phase can nowadays be characterized with sufficient accuracy, this is no longer the case for particles in the presence of a complex biological environment. Interactions between nanoparticles and biomolecules are highly complex on a molecular scale. The detailed characterization of nanoparticles under these conditions and the mechanistic knowledge of their molecular interactions with the biological world is, however, needed for any solid conclusions with regards to the relationship between the biological behavior of such particles and their physicochemical properties. In the present article we discuss some of the challenges with characterization and behavior of nanoparticles that are associated with their presence in chemically complex biological environments. Our focus is on the stability of colloids as well as on the formation and characteristics of protein coronae that have recently been shown to significantly modify the properties of pristine particles. Finally, we discuss the perspectives that may be expected from an improved understanding of nanoparticles in biological media.
Subject(s)
Colloids/chemistry , Nanoparticles/chemistry , Proteins/chemistry , Chemical Phenomena , Surface PropertiesABSTRACT
The expression of nerve hemoglobins in invertebrates is a well-established fact, but this occurrence is uncommon. In the species where nerve globins occur, they probably function as an oxygen store for sustaining activity of the nerves during anoxic conditions. Although invertebrate nerve globins are functionally similar with respect to O2 affinity, they are by no means uniform in structure and can differ in size, cellular localization and heme-coordination. The best-studied nerve globin is the mini-globin of Cerebratulus lacteus, which belongs to a class of globins containing the polar TyrB10/GlnE7 pair in the distal pocket. The amide and phenol side chains normally cause low rates of O2 dissociation and ultra-high O2 affinity by forming strong hydrogen bonds with bound ligands. Cerebratulus hemoglobin, however, has a moderate O2 affinity, due to the presence of a third polar amino-acid in its active site, ThrE11, which inhibits hydrogen bonding to bound oxygen by the B10 tyrosine side chain.
Subject(s)
Globins/metabolism , Nervous System/metabolism , Animals , Mollusca/metabolism , Protein Structure, TertiaryABSTRACT
Myoglobin, a small globular heme protein that binds gaseous ligands such asO(2), CO and NO reversibly at the heme iron, provides an excellent modelsystem for studying structural and dynamic aspects of protein reactions. Flashphotolysis experiments, performed over wide ranges in time and temperature, reveal a complex ligand binding reaction with multiple kinetic intermediates, resulting from protein relaxation and movements of the ligand within the protein. Our recent studies of carbonmonoxy-myoglobin (MbCO) mutant L29W, using time-resolved infrared spectroscopy in combination with x-ray crystallography, have correlated kinetic intermediates with photoproduct structures that are characterized by the CO residing in different internal protein cavities, so-called xenon holes. Here we have used Fourier transform infrared temperature derivative spectroscopy (FTIR-TDS) to further examine the role of internal cavities in the dynamics. Different cavities can be accessed by the CO ligands at different temperatures, and characteristic infrared absorption spectra have been obtained for the different locations of the CO ligand within the protein, enabling us to monitor ligand migration through the protein as well as conformational changes of the protein.
ABSTRACT
We examined the effectiveness of a high-dose Immunglobulin therapy in 8 patients with idiopathic thrombocytopenic purpura (ITP) and measured the number, the morphology and the function of Thrombocytes as well as thrombocyte dependent clotting parameters. 0.5 g/kg/B.W. 7s-Immunglobulin (7s-IgG) per treatment led to normal thrombocyte numbers in 7 out of 8 patients. The maximal thrombocyte-rise occurred on the 4th-10th day of treatment. Simultaneously bleeding time, thrombocyte-volume distribution frequency and Ristozetin-ADP and Collagen induced thrombocyte-aggregation normalized-indication as well as cause of the 7s-IgG-therapy are discussed.
Subject(s)
Blood Platelets/drug effects , Immunoglobulin G/administration & dosage , Purpura, Thrombocytopenic/drug therapy , Adolescent , Bleeding Time , Blood Coagulation Tests , Child , Child, Preschool , Female , Humans , Male , Platelet Aggregation/drug effects , Platelet Count , Purpura, Thrombocytopenic/bloodABSTRACT
Determination of blood traumatization by extracorporeal circulation systems (ECC) in clinical trials may be interfered with by the underlying heart disease, by priming the circuit with blood or plasma expanders and by different operation techniques requiring a variable amount of coronary suction. Therefore, in this study a standardized animal model was used to compare blood traumatization in 2 bubble and 2 membrane oxygenators. After 2 hours of extracorporeal circulation, there was no advantage of the membrane over the bubble oxygenators concerning hemolysis, platelet preservation and induction of clotting factors. Red cells and platelets were traumatized in membrane oxygenators during the first 30 minutes without a significant further increase, whereas blood trauma in bubble oxygenators increased until bypass was disconnected. Therefore bubble oxygenators appear better suited for shorter perfusions, whereas membrane oxygenators are the superior choice in perfusions lasting longer than 2 hours.
